Brain function has been implicated to control the aging process and modulate lifespan. However, continuous efforts remain for the identification of the minimal sufficient brain region and the underlying mechanism for neuronal regulation of longevity. Here, we show that the Drosophila lifespan is modulated by rab27 functioning in a small subset of neurons of the mushroom bodies (MB), a brain structure that shares analogous functions with mammalian hippocampus and hypothalamus. Depleting rab27 in the α/βp neurons of the MB is sufficient to extend lifespan, enhance systemic stress responses, and alter energy homeostasis, all without trade‐offs in major life functions. Within the α/βp neurons, rab27KO causes the mislocalization of phosphorylated S6K thus attenuates TOR signaling, resulting in decreased protein synthesis and reduced neuronal activity. Consistently, expression of dominant‐negative S6K in the α/βp neurons increases lifespan. Furthermore, the expression of phospho‐mimetic S6 in α/βp neurons of rab27KO rescued local protein synthesis and reversed lifespan extension. These findings demonstrate that inhibiting TOR‐mediated protein synthesis in α/βp neurons is sufficient to promote longevity.

中文翻译：

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Rab27对苍蝇蘑菇体α/β后神经元的寿命调节。

大脑功能与控制衰老过程和调节寿命有关。然而，仍在不断努力确定最小的足够大脑区域和长寿神经元调节的潜在机制。在这里，我们表明果蝇的寿命受rab27调节，在蘑菇体 (MB) 的一小部分神经元中起作用，蘑菇体 (MB) 是一种与哺乳动物海马和下丘脑共享类似功能的大脑结构。消耗MB的 α/βp 神经元中的rab27足以延长寿命、增强全身应激反应和改变能量稳态，所有这些都不会影响主要生命功能。在 α/βp 神经元内，rab27KO导致磷酸化 S6K 的错误定位，从而减弱 TOR 信号传导，导致蛋白质合成减少和神经元活动减少。一致地，α/βp 神经元中显性负性 S6K 的表达延长了寿命。此外，rab27KO α/βp 神经元中磷酸模拟 S6 的表达挽救了局部蛋白质合成并逆转了寿命延长。这些发现表明，抑制 α/βp 神经元中 TOR 介导的蛋白质合成足以延长寿命。